The only known natural host of measles virus (MV) is humans. Although an effective vaccine exists, MV is a major health problem with over 40 million cases and one million fatalities annually. Mortality occurs mainly from the profound immunosuppression that accompanies MV infection associated with secondary bacterial, fungal or parasitic infection and from encephalomyelitis. In rare cases, MV persistently infects the CNS causing a progressive, uniformly fatal disease SSPE. Understanding how measles virus causes disease and design of therapeutic modalities or a new vaccine have been hampered in the past by a lack of a suitable small animal model. To overcome this difficulty we created mouse models in which MV effect on the immune system and the CNS could be studied and manipulated. This was accomplished using transgenic (tg) mice expressing the human (h) MV receptor, CD46 (Cell 98:629, 1999; PNAS 94:4659, 1997) or SLAM (this tjrant). With tg mice expressing hCD46, hSLAM and CD46 x SLAM, and recombinant MV expressing GFP, we anticipate following how MV spreads from the nasal/upper respiratory tracts throughout the body, how it spreads from neuron to neuron in the CNS, analyze rnolecularly and physiologically MV-neuronal interactions on population of neurons (hippocampal slices) and on singles green fluorescing neurons. We will study immunosuppression focusing on MV interactions with the innate and adoptive immune system in the presence and absence of bacterial infection. Use of mice with various components of the innate and adoptive immune system genetically deficient, a system for generating recombinant MVs, tg mice that express MV receptors ubiquitously or specifically in neurons, in T cells and in dendritic cells should allow a molecular definition for better undemanding of both viral and host factors contributing to disease and ways of altering viral infection and viral-induced disease.